The overall objective is to develop and refine biophysical methods to separate homogenous populations of cells from the heterogeneous population comprising various solid tumors and to characterize these populations of cells with respect to their clonogenicity and their response to ionizing radiation. The in vivo tumor systems which will be studied include: a methylcholanthrene-induced fibrosarcoma, a spontaneously arisen mammary carcinoma, a L-P59 sarcoma and a teratoma, as well as two in vitro tumor "model" systems of cultured mammalian cells. The cell separation methods used include the separation of cells on the basis of their buoyant density by means of centrifugation in continuous and linear density gradients and on the basis of their size by means of velocity sedimentation at unit gravity. Cell clonogenicity will be assayed in vivo using a lung colony assay and in vitro using standard tissue culture methods. The response of each of the separated clonogenic cell populations to exposure to single doses of ionizing radiation and to certain radiation sensitizing electron-affinic drugs will be studied. Each of the separated tumor cell populations will be assayed to determine their relative capabilities to accumulate and repair sublethal and potentially lethal radiation damage.